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bioRxiv · 10.1101/2023.06.18.545497

An EGF-modified PLGA-lanthanide nano platform for combined NIR-II cancer imaging and targeted drug delivery

He, Y.·Yu, z.·Schomann, T.·Zhang, H.·Eich, C.·Cruz, L. j.
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Abstract

The use of multifunctional nanoplatforms for synergistic therapy and imaging is a promising approach in cancer treatment. In this study, we exploited the imaging properties of lanthanides by encapsulating CaF2:Y, Nd along with the chemotherapeutic drug doxorubicin (DOX) into poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to prepare a nanoplatform suitable for imaging in the second near-infrared (NIR-II) window and simultaneous anti-cancer therapy. To facilitate the accumulation of CaF2:Y, Nd+DOX@PLGA NPs in breast cancer cells, we modified the NPs with EGF. The diameter of the obtained CaF2:Y, Nd+DOX@PLGA/PEG/EGF NPs was approximately 150 nm, with a nearly round shape and homogeneous size distribution. In addition, analysis of the drug release behaviour showed that DOX was released more readily and had a longer release time in acidic environments. Accordingly, MTS results indicated that DOX-loaded NPs were significantly cytotoxic. Furthermore, fluorescence microscopy and flow cytometry studies revealed that CaF2:Y, Nd+DOX@PLGA/PEG and CaF2:Y, Nd+DOX@PLGA/PEG/EGF NPs were gradually taken up by 4T1 breast cancer cells over time, and EGF-coated Nd+DOX@PLGA NPs exhibited increased uptake rates after 72 h. Moreover, we found that EGF increased the solubility of Nd+DOX@PLGA NPs in water by comparing the aqueous solutions of the different NPs formulations. Finally, NIR imaging demonstrated strong fluorescence of PLGA NPs carrying CaF2:Y, Nd NPs at 900-1200 nm under 808 nm laser excitation. In conclusion, the developed CaF2:Y, Nd+DOX@PLGA/PEG/EGF NPs could be monitored for an extended period of time, and co-encapsulated DOX could be efficiently released to kill breast cancer cells.

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He, Y., Yu, z., Schomann, T., Zhang, H., Eich, C., Cruz, L. j.. 2023-06-21. An EGF-modified PLGA-lanthanide nano platform for combined NIR-II cancer imaging and targeted drug delivery. https://doi.org/10.1101/2023.06.18.545497

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